Work

Mixed Myeloid Chimerism and Hemolytic Markers After Nonmyeloablative HCT for Sickle Cell Disease

Year: 2026

Type: article

Abstract: Sickle cell disease (SCD) is a hemolytic anemia characterized by both intravascular and extravascular hemolysis. Allogeneic hematopoietic cell transplantation (allo-HCT) can be curative in SCD, including in the setting of mixed donor myeloid chimerism. Despite resolution of sickle-related disease complications and chronic anemia following allo-HCT, laboratory evidence of hemolysis may persist. The relationship between mixed myeloid chimerism and residual hemolysis remains incompletely defined and may have implications for newer genetic therapies where a portion of host hematopoietic stem cells remain uncorrected. We evaluated the association between donor myeloid chimerism and hemolytic indices—absolute reticulocyte count (ARC), lactate dehydrogenase (LDH), total bilirubin, and aspartate aminotransferase (AST)—in 88 adult patients with SCD following nonmyeloablative matched-related donor allo-HCT ( ClinicalTrials.gov ID: NCT00061568, NCT02105766). Seventy-three recipients were evaluable at a median follow-up of 5.74 years (range, 1.5-16.97), including 35 (46%) with mixed myeloid chimerism (5-95%). Hemolytic indices inversely correlated with donor myeloid chimerism in the mixed chimerism cohort, reaching statistical significance for all markers except LDH. Although all indices improved compared with pre-HCT values, patients with lower donor chimerism demonstrated higher residual hemolysis, with ARC significantly elevated in the ‘Mixed Low’ (20–50%) compared with ‘Mixed High’ (51–95%) cohort. ARC and LDH remained significantly lower in the ‘Mixed Low’ cohort compared to those with graft failure. Our findings demonstrate a negative correlation between donor myeloid chimerism and residual hemolysis following nonmyeloablative allo-HCT, supporting biologically relevant thresholds of corrected hematopoiesis that may help inform gene therapy approaches in SCD.

Source: Blood Red Cells & Iron

DOI: 10.1016/j.brci.2026.100118

Authors: Zaina Inam, Francis J Pierciey, Matthew Hsieh, Alexis Leonard, Selami Demirci, John Tisdale